Automated system and method of processing biological specimens

ABSTRACT

An apparatus including at least one of a stainer module and a coverslipper module; an imaging module; a storage module; an automated transport module for transporting at least one slide between at least one of the stainer module and the coverslipper module, the imaging module and the storage module; and a controller. A method including processing at least one slide; determining whether an imaging module is available for imaging of a biological specimen on the at least one slide; transporting the at least one slide to the imaging module using an automated transport module; and transporting the at least one slide to a storage module using the automated transport module when it is determined that the imaging module is not available. A system including a processing module for processing at least one slide including a biological specimen thereon. A machine readable medium.

BACKGROUND

1. Field

An automated system of processing biological specimens.

2. Background

In various settings, examination of biological specimens is required fordiagnostic purposes. Generally speaking, pathologists and otherdiagnosticians collect and study samples from patients, and utilizemicroscopic examination, and other devices to assess the samples atcellular levels. Numerous steps typically are involved in pathology andother diagnostic process, including the collection of biological samplessuch as blood and tissue, processing the samples, preparation ofmicroscope slides, staining, examination, re-testing or re-staining,collecting additional samples, re-examination of the samples, andultimately the offering of diagnostic findings. Numerous medical orveterinary personnel may be involved in the diagnostic processes,including surgeons, phlebotomists or other operating personnelcollecting samples, pathologist, histologists and other personnelprocessing, transporting and examining the samples and so on. Thecomplexity of the tissue handling procedures from the operating room tothe laboratory and back to the diagnosticians or surgeons have becomeincreasingly complex in large medical environments where high volumes ofsamples need to be handled, processed and examined on a daily basis.

Various steps of the tissue handling procedures have been automatedusing instruments each of which typically are controlled by a dedicatedcomputer or an on-board computerized controller. In some laboratories,information can be shared between automated instruments and/or anetworked laboratory or hospital information system, such as to storepatient or tracking data. One example of an automated instrument is anautomated tissue processing system in which biological samples are fixedand infiltrated with paraffin in an automated fashion. Exemplary tissueprocessing systems are the TISSUE-TEK® VIP® and the TISSUE-TEK® XPRESS®processing systems available from Sakura Finetek U.S.A., Inc. ofTorrance, Calif.

Another example of automation is an automated microscope slide stainerand coverslipper, which stains microscope slides and applies coverslipsto the slides in an automated fashion. Examples of such automatedstaining and coverslipping systems are TISSUE-TEK® PRISMA® andTISSUE-TEK® FILM® combo system and TISSUE-TEK® PRISMA® and TISSUE-TEK®Glas™ g2 combo system available from Sakura Finetek U.S.A., Inc. ofTorrance, Calif.

Despite the assistance of automated instruments, pathologists, otherdiagnosticians and laboratory personnel typically must be involved innumerous steps during the processing and examination of biologicalsamples. For example, once a sample has been stained, the stained sampleon a microscope slide may be physically examined under a microscope.This typically involves transport of the microscope slide to adiagnostician who is located outside the laboratory, or in other casesmay involve a diagnostician going to the laboratory to examine themicroscope slide. Alternatively, the stained sample on a microscopeslide is imaged with a digital camera and the image of the sample isuploaded for examination by a diagnostician.

Following this initial examination step, the diagnostician evaluateswhether additional testing is required. Such additional testing mightinvolve collecting further samples from a patient, or further testing ofsamples already collected. For example, the diagnostician may requirethat the existing sample be sectioned further and a different stainingregimen or other protocol be applied. This can result in iterations ofone or more of collection, grossing, processing, infiltration,embedding, sectioning, coverslipping, staining, examination etc. Inaddition, different coverslipped slides may require different dryingtimes. Accordingly, some slides may be ready for examination whileothers are not. All of this can result in time delays, as well as tissueimpairment. Following the iterations of additional tests and procedures,the pathologist repeats the examination process, and may then requeststill further tests in an iterative fashion until an ultimate finding isreached. Even with automated instruments in these processes, there arenumerous transport, and human interventions required.

BRIEF DESCRIPTION OF THE DRAWINGS

The embodiments of the invention are illustrated by way of example andnot by way of limitation in the figures of the accompanying drawings inwhich like references indicate similar elements. It should be noted thatreferences to “an” or “one” embodiment in this disclosure are notnecessarily to the same embodiment, and such references mean at leastone.

FIG. 1 is a flow chart of one embodiment of a method for automaticallyprocessing biological specimens.

FIG. 2 illustrates one embodiment of an automated system for processingbiological specimens.

FIG. 3 illustrates one embodiment of an automated system for processingbiological specimens.

FIG. 4 illustrates a top view of one embodiment of an automated systemfor processing biological specimens.

FIG. 5 illustrates a side view of the automated system of FIG. 4 throughline 5-5′.

FIG. 6 illustrates a side view of the automated system of FIG. 4 throughline 6-6′.

FIG. 7 illustrates a top view of the automated system of FIG. 4 showinga slide placed in an imager.

FIG. 8 illustrates a side view of the automated system of FIG. 4 throughline 8-8′.

FIG. 9 shows a perspective view of an embodiment of a storage module ofthe automated system of FIG. 4.

DETAILED DESCRIPTION

In the following paragraphs, the present invention will be described indetail by way of example with reference to the accompanying drawings.Throughout this description, the preferred embodiments and examplesshown should be considered as exemplars, rather than as limitations onthe present invention. As used herein, the “present invention” refers toany one of the embodiments of the invention described herein, and anyequivalents. Furthermore, reference to various aspects of the inventionthroughout this document does not mean that all claimed embodiments ormethods must include the referenced aspects.

In overview, a system and process for performing a series of automatedoperations including tissue processing, imaging and tissue storage isdisclosed. FIG. 1 shows a flow chart of one embodiment of a processimplemented by a system (i.e., machine-readable program instructionsimplemented in a processor connected to process control modules). Asillustrated in block 102, process 100 includes obtaining at a materialhandling system a biological sample that has been mounted on a slide.The biological sample is conveyed to a material handling system, forexample by manual transport, a cart or automated transport. In ahospital embodiment, the specimen may be delivered to a medicallaboratory, whether on-site or at a remote location.

At the material handling system, the slide mounted specimen may beprocessed via automated operations into a condition suitable for adesired examination. In one embodiment, processing includes staining thebiological sample and applying a cover slip to the slide (block 104).Staining of the specimen may be optional. The slide having the specimenthereon is then transferred to a transport module (block 106). In someembodiments, the slide is transferred to the transport module using arobotic transferring device as will be discussed in more detail inreference to FIGS. 4-9.

Process 100 further includes determining whether the slide is ready forimaging (block 108). Such a determination may be based on, for example,the drying time of the slide. For example, different methods ofcoverslipping exist and each one requires different drying times.Representatively, a glass cover slip may require about a day to drywhile a film cover slip may dry in about an hour. In this aspect,coverslipped slides that are not ready (e.g. not dry) for furtherprocessing (e.g., imaging) are transported to a storage module to givethem additional time to dry (bock 112). Slides that are dry aredetermined to be ready for imaging.

Process 100 further includes determining whether the imager is availablefor imaging (block 110). Imaging of a specimen on a slide typicallytakes longer than the amount of time it takes to stain, coverslip anddry the slide, because imaging must be done on individual slides (i.e.,one at a time) while staining and coverslipping operations may be doneon a number of slides at the same time (e.g., staining a batch ofslides). For example, slide imagers can perform a 20× scan of a 15×15 mmtissue in about 2½ to 3 minutes. Higher resolution and z-stackingrequirements can double that time. This equates to an imager throughputof from about 10-24 slides per hour. In contrast, up to about 500 slidesper hour may be processed through a coverslipper and/or stainer. As aresult, the imager is often times not ready to image each of the slidesas they exit the coverslipper and/or stainer. If the imager is notavailable, the slides are transported from the coverslipper to a storagemodule for storing until an imager is available (block 112).

Once the imager is available, the slide is transported to the imager(block 114) for imaging. At the imager, a digital image of the specimenis captured and stored in a computer memory. After a specimen, or groupof specimens, is prepared for examination, the specimen(s) may beexamined and the data may be made available to a diagnostician and/or anoptional interpretation module which automatically interprets the data(block 116). It should be noted that, as used herein, “diagnostician”refers to any person who may wish to view image data, such aspathologists, surgeons, nurses, researchers, technicians andadministrators.

Image data may be created, such as using a digital imager including, forexample, a CCD technology. The image data preferably is made availablefor access by a diagnostician if desired, and optionally thediagnostician is notified such as by electronic notification, such as byan e-mail, computer screen pop-up announcement, banner announcement,pager message or automated phone call. In other embodiments, the imagedata may also be accessed, or otherwise made available, to an optionalinterpretation module. The interpretation module may conduct digitalprocessing, such as by using pattern recognition technology in order todevelop a preliminary diagnosis, and generate instructions orrecommendations for additional processing.

The additional processing, illustrated with block 118, may includecollecting additional biological samples, or performing furtherprocessing on samples already collected such as running additional ordifferent test procedures or staining protocols. For example, afterimaging, a specimen may be transported by the transport module to thestorage module. The specimen image may be examined, and if it isdetermined that further imaging is necessary, the specimen is retrievedfrom the storage module by the transport module and transported to theimager for imaging. Examination, imaging and interpretation of thesample may be continued until the system or diagnostician deems it to becomplete. These repeated tests and examinations are referred to hereinas iterative processing, testing or examination. In another aspect ofthe invention, the diagnostician may access reports that are based onthe comparison data created by the interpretation module. In a furtheraspect of the invention, the diagnostician may order or conduct furtheriterative processing, testing or examination.

FIGS. 2-9 illustrate examples of automated systems for processingbiological specimens. In these figures, information pathways areillustrated with solid lines and/or arrows and material pathways areillustrated with double lines and outlined arrows. As used herein,“material” refers to any biological material including histological andcytological specimens that may be examined in a medical, autopsy,veterinary or research laboratory procedure. The biological material mayinclude tissue samples or specimens, and/or biological fluids such asblood, plasma, etc. Although the illustrated examples are described inrelation to tissue, the described systems and methods are not solimited. As used herein the biological material will be referred tointerchangeably as a specimen, sample or material. In addition,references relating to processing of a “slide” herein refer to a slidehaving the biological material thereon.

In the illustrated examples, the material pathways represent examples oftransport paths that may be traveled by a physical sample in alaboratory or hospital. A typical progression of the material from onestation or system component to the next is depicted by the direction ofthe arrow. However, it should be understood that the processing stationsare provided as examples, as are the directions of material flow. Itshall be appreciated that more, fewer or other processing stations maybe used in practice of the present invention, and/or more, fewer orother material paths and directions may be used in the practice of thepresent invention. In addition, the stations may be in any order and anyorientation (e.g. vertically stacked or side by side).

Any form of transport may be used that is sufficient to automaticallytransport the material as indicated by the material pathways. Forexample, material may be transported by a robotic device from onestation to the next as will be discussed in more detail in reference toFIGS. 4-7. The term robot or robotic is to be interpreted broadly as aconveyance, transfer device, electro-mechanical transfer device ormechanism, or automatically controlled, reprogrammable, multipurposemanipulator programmable in three, four, or more axes. The roboticdevice may take various forms or configurations, consistent with itsintended purpose. The robotic device may be programmed with anapplication program, program routine, or other set of instructions. Theprogram or set of instructions may specify one or more operations therobotic device is to autonomously or at least semi-autonomously perform.Representatively, the program or set of instructions may specify themovements (e.g., coordinates, distances, directions, etc.), timing ortriggers, and like information associated with the operations. In someembodiments, the material may also, or alternatively, be hand carriedfrom one station to the next. Additionally, one machine may performmultiple steps with no physical movement of the material from onestation to another being required.

In the embodiment of FIG. 2, a specimen mounted on a microscope slide istransported to staining module 210. Prior to transporting the specimento staining module 210, the specimen may be processed through, forexample, a grossing station (in the case of non-fluid specimens), atissue processor where the specimen is treated with a series ofreagents, an embedding station where it may be infiltrated with paraffinand embedded and a microtome station where the specimen is sectioned.Specimen sections created in the microtome station are positioned on themicroscope slide. Slides requiring deparaffinization may be placed in anoven prior to staining, or placed directly in the stainer if the staineris equipped with a built-in oven or can perform a chemicaldeparrafinization step.

Any staining or other test protocol may be performed by the stainingmodule 210 as desired. In one embodiment, an automated stainer is used.In an example, staining with hematoxylin and eosin (“H & E”) isperformed in staining module 210. Other staining methods such as specialstains (SS), immunohistochemistry (IHC), and in situ hybridization (ISH)can also be performed.

In one embodiment, following staining, the samples may be transportedalong material path 217 to coverslipper module 220 to be coverslipped.

After staining and/or coverslipping, the slide may proceed to imager 230or storage module 202. In some embodiments, where it is desirable forimaging of the slide to be delayed, the slide is transported to storagemodule 202 for storage until imaging is desired. Representatively,different methods of coverslipping exist and each one requires differentdrying times. Coverslipped slides that are not ready (e.g. not dry) forfurther processing are transported to storage module 202 along materialpath 203. Once the slides are ready, they may then be transported alongmaterial path 205 to imager 235. In this aspect, the differences indrying times from slide to slide are automatically resolved by theautomated system.

In some embodiments, the laboratory can select delay criteria based onthe coverslipping technique used and the type of sample (histology v.cytology, monolayer slides v. smears, etc.). For example, the laboratorymay determine, based on the coverslipping technique to be used and thetype of sample on the slide, that the slide should be stored for aperiod of time prior to imaging. This information may be contained in anidentifier associated with the slide. Examples of identifiers include aradio frequency identification (RFID) tag, barcode that may be read by areader associated with the system that provides information to theautomated system. The automated system may read the identifier andfollow the assigned processing protocol. In this aspect, aftercoverslipping, the slide is transported to storage module 202 and storedfor the predetermined period of time. After such time, the system mayalert the transport module to retrieve the slide from storage module 202and transport the slide to imager 230 for imaging.

In addition to drying times, the availability of imager 230 may furtherdelay imaging. In particular, imaging of a specimen on a slide typicallytakes longer than the amount of time it takes to stain, coverslip anddry the slide. For example, current commercially available slide imagerscan perform a 20× magnification scan of a 15×15 mm tissue in about 2½ to3 minutes. Higher resolution and z-stacking requirements can double thattime. This equates to an imager throughput of from about 10-24 slidesper hour. In contrast, up to about 500 slides per hour may be processedthrough the stainer/coverslipper modules. As a result, the imager isoften times not ready to image each of the slides as they exit thestainer/coverslipper modules. The identifier associated with the slidemay store information regarding the desired imaging protocol for theslide (e.g., a 10× scan, a 20× scan or a 40× scan). Upon reading theidentifier, the system schedules imaging of the slide with an imagercapable of imaging at the desired magnification. If the desired imageris not available when the slide is otherwise ready for imaging, theslide is transported from staining module 210 and/or coverslipper module227 along material path 203 to storage module 202 for storing untilimager 230 is available.

It is further contemplated that after a specimen is imaged by imager230, the specimen slide may be transported along material path 205 tostorage module 202. The slide may be stored in storage module 202 forfuture testing and/or examination.

Once the specimen is ready for imaging, at least one image of thematerial specimen is obtained by imager 230. The imaging protocol foreach slide which is to be followed by imager 230 may be flexible and canbe defined at any time by, for example, the diagnostician (e.g.,pathologist). In this aspect, the diagnostician can have real timecontrol of the imaging process remotely. For example, a pathologist mayexamine an image and determine that additional images of the slide arenecessary. Representatively, the pathologist may determine that imagesat a different magnification are necessary or that the imager shouldfocus deeper into a tissue area. According to the automated systemdisclosed herein, the pathologist may instruct the system to obtainfurther images. The system will then automatically retrieve the specimenfrom storage module 202 and transport it to imager 230 for furtherimaging as requested. The pathologist may receive the results the sameday as the request, as opposed to current imaging systems which oftenprocess highest resolution and z-stacking images overnight.

Imager 230 may include one or more imagers. The imager can be any systemthat generates images that can be interpreted manually interpreted or,optionally, automatically interpreted by interpretation module 290. Inthe illustrated embodiment, imager 230 includes a microscope and acamera capable of recording digital images of the microscope's viewfield. For example an optical CCD based camera can be used to generatethe digital image data. The digital image data can be stored in anyfashion that provides for access to the data as required byinterpretation module 290, diagnostician work station 240 and/ortechnician work station 250 and/or as desired by anyone needing accessto the image data, such as diagnosticians or laboratory personnel.Examples of suitable data storage are local storage devices associatedwith imager 230 (such as hard drive, removable memory, flash memory,optical memory such as CD or DVD etc.), and/or networked memory such asdiagrammatically illustrated by data storage 260. It should be notedthat any form of information may be generated by imager 230, in additionto the image data. For example, imager 230 may optionally associateother types of data, such as a log of patient information associatedwith the image data and as discussed further herein. Alternatively,another processing system may associate the image data with other data.

In one embodiment, the type of information generated is intended to besufficient for interpretation module 290 to perform its interpretationprocessing and generate the desired report. Interpretation module 290may take any desired form, such as for example, a dedicated computingsystem, or alternatively it may be a module running on a computingsystem used for multiple purposes. In additional examples, it may befreestanding, a part of imager 230, part of hospital information system270, part of laboratory information system 280, or it may be in anylocation where data may be received from imager 230. Although the figuredepicts a single interpretation module 290, it should be understood thatplural interpretation modules 290 also may be used. In further examples,diagnostician work stations 245 may include interpretation modules 290or interpretation module clients that enable the diagnostician tolocally conduct an interpretation based on the data available including,without limitation, image data from imager 230.

In the embodiment of FIG. 2, interpretation module(s) 290 is incommunication via communications infrastructure 200. Interpretationmodule 290 may access data as desired, whether directly from imager 230,via data storage facility 260, or via local data storage. Interpretationmodule uses the image data and other data to perform an analysis and arecommendation. In an embodiment, the analysis includes a patternrecognition analysis in a pattern recognition system of interpretationmodule 290. In one form of pattern recognition, image data from imager230 is compared to a database of known patterns. If a sufficient levelof correspondence is found, a matching pattern is located upon which arecommendation, diagnosis or further processing instruction can be made.The pattern database can be a part of interpretation module 290, orlocated externally, such as for example in data storage 260 orlaboratory information system 280.

Following imaging by imager 230, interpretation module 290 may beconfigured to determine if the imaged sample should go to storagemodule, in which case it proceeds along material pathway 227, orinterpretation module 290 may be configured to determine whether theparticular sample needs to undergo additional processing, such as thatit should go to a diagnostician or other personnel for personalinspection, in which case it proceeds along material pathway 237.

Alternatively, interpretation module 290 may be configured to determineif further processing of the tissue represented by the imaged sample isrequired. In such case, a new sample of the tissue is necessary forinterpretation. In one embodiment, additional section(s) (samples) ofthe same tissue may have been placed on slide(s) and those slide(s) sentto storage module 202 with a label that links the slide(s) to the imagedsample. In this embodiment, the slide(s) are not stained orcoverslipped, and are kept aside. These slides could be identified asbeing extra sections that should not be stained and kept in the storagearea until called back for staining and coverslipping. For example,these extra slide(s) may have the same identification information as theoriginal or primary, perhaps with an additional indicator (e.g., anadditional letter or number) to indicate the slide(s) are extraslide(s). If they are not needed, these slides can be discarded after,for example, a user-defined period of time has elapsed or the case hasbeen completed and signed off. Extra sections are cut and extra slidesprepared and stained only when there is a requirement for more stainingprotocols. In an automated handling system that also includes handlingof tissue blocks, the request for more staining would be transferred tomicrotomy module 205. In one embodiment, a tissue block, including aformalin-fixed tissue section in a paraffin block from which anothertissue section may have been taken and placed on a slide, includes anidentification tag such as a bar code or RFID tag. In response to asignal from a controller, the tissue block is retrieved and transportedautomatically from a storage module (e.g., storage module 202) tomicrotomy module 205. The tissue block is stored and may be retrieved bythe identification tag. The tissue block would be forwarded to themicrotomy area for more sections to be taken.

Representatively, once a new sample is placed on a slide, the new sampleproceeds to stainer module 210 where it may undergo operations such asspecial staining, immunohistochemistry (“IHC”), in situ hybridization(“ISH”), multiplexing or other staining or testing procedures.Subsequently, the new sample may proceed along the material path, forexample, back to imager 230. Ultimately it is desired that a tested andimaged sample be stored as indicated by storage module 202. In thisexample, after inspection by a diagnostician or other person, theoriginal sample may be designated for storage, such as in storage module202 and the new sample from the same tissue section designated andfurther processed. The new sample may be processed and inspected andsent to storage The original sample and the new sample are linked by anidentification tag. Later, either or both the original and the newsample can optionally be retrieved from the storage module 202, ifdesired.

The work stations, such as diagnostician work stations 240 or other workstations, such as technician work stations 250 can have any desiredstructure, including computing systems serving as controllers incommunication via communications infrastructure 200 with otherprocessing stations or components of the system. The work stations mayoptionally also include other components that might be useful in a workarea, such as material storage units, furniture, phones etc. In anembodiment, the work stations 240, 250 provide access to informationconcerning the processing of biological samples, and the results of theprocessing, including image data from the imager 230 and interpretationdata or reports from the interpretation module 290. Technician workstation 250 may be in communication with data storage 260 via path 257.In another embodiment, a system may not include work stations such asdiagnostician work stations 240 and/or technician work stations 250.

As the material proceeds along the material pathways and through theprocessing systems, information may be shared between the numerousdevices using various information pathways that form communicationsinfrastructure 200. It should be noted that communicationsinfrastructure 200 may be any form of communication system enablingcommunications between and amongst individuals, computer systems and/orautomated processing systems. Representatively, the communicationsinfrastructure may be a computer network that is wired, wireless or acombination of wired and wireless. For example, information accesspoints may be wired into the network and/or joined to the network via awireless portal. Although the illustrated example shows a networkedsystem in which communications are performed via a network, directcommunications also may be conducted. For example in one embodiment,staining module 210 may have a direct communications link withcoverslipper module 220 and may access the communications network via anode in coverslipper module 220, or alternatively it may have a directnetwork link. It should be understood that any suitable communicationspathway structure is envisioned which would enable suitable sharing ofinformation between and amongst various stations. Likewise, it should beunderstood that, in other embodiments, not all of the stations may havea direct communications path. Furthermore, it should be understood thatthe communication pathways can take any form, such as digital, analog,wired, wireless, paper, oral, telephonic, etc.

In one embodiment, a laboratory network may be provided as the portionof the communications infrastructure 200 between and amongst thelaboratory instruments, depicted with reference numbers 210, 220, 230,202 and also laboratory information system 280 and other work stations240 and 250 (which might include a computer system such as for exampleone or more personal computers and/or computer servers). The laboratorynetwork may be networked with a hospital network that is also a part ofcommunications infrastructure 200. In such an embodiment, other devicesmay have access to the information available on laboratory informationsystem 280 or other laboratory devices via the communicationsinfrastructure 200. Such other devices include for example,diagnostician or administrator work stations 240, hospital informationsystem 270, and in some embodiments interpretation module 290 as well.It should be understood that the flexibility of the information pathwaysis directed to enable the necessary information flow to track biologicalsamples being processed however desired, and to distribute the necessaryinformation to the appropriate users. Numerous alternativecommunications system structures may be selected to meet this need, andthe illustrated and discussed examples are provided for illustrativepurposes only, not to limit the scope or flexibility of the system.

Referring to the illustrated example, communications pathways 203, 205,207, 215, 225, 235, 245, 255, 265, 275, 285, 295, represent examples ofcommunications pathways between staining module 210, coverslipper module220, imager 230, storage module 202, diagnostician work station 240,technician work station 250, local or remote data storage 260 and/orhospital information system 270, laboratory information system 280,interpretation module 290, or any other desired station or component ofthe system.

The sharing of information may be automated, manual or conceptual. Forexample, information may be shared directly by two machines incommunication with each other, it may be made available to a user whocan manually input it into another device, or a single machinecomprising more than one device shown in FIG. 2 can engage in internalcommunication. This sharing of information often involves two-waycommunication. For example, images from a patient having a chroniccondition may be sent to a database of patient information storage, andpreviously obtained information regarding the same patient may beretrieved from the database in order to monitor the progression of thecondition. In another embodiment, each station in the material path iscapable of communicating via the communications infrastructure 200 andthe stations may communicate the progression of the material along thematerial pathways as well as other information, as discussed in furtherdetail below.

In another embodiment, biological specimens, slides, trays, containers,workpieces, and locations throughout the system may be identified withmachine understandable codes, such as provided by RFID tags, shapeidentifiers, color identifiers, numbers or words, other optical codes,barcodes etc. The identifiers can be recorded to generate data providedto a database, such as data maintained in data storage device 260, by aprocessor (any computing devices), hospital information system 270,laboratory information system 280 or any combination thereof. Examplesof data that may be tracked include patient information and history,information regarding biological sample(s) collected, arrival anddeparture times of biological samples, tests performed on the samples,processes performed on the samples, reagents applied to the samples,diagnoses made, associated images and so on.

FIG. 3 illustrates an embodiment of a system for automaticallyprocessing a biological specimen. System 300 includes transport module302. Transport module 302 may automate, or at least partially automate,the transfer of slides or other tissue holders between the stations,namely between one or more of staining module 304, coverslipper module306, imagers 308, 310, 312, storage module 314 and microtomy module 307.Automatically transporting slides or other tissue holders betweenstaining module 304, coverslipper module 306, imagers 308, 310, 312storage module 314, and microtomy module 307 as opposed to manuallytransferring the slides or other tissue holders, offers certainpotential advantages. For one thing, it may free personnel from thenecessity of having to performing these sometimes repetitive or tediousoperations manually. Advantageously, this may allow the personnel toperform more value-added operations and/or other operations lessamenable to automation. For another thing, the transport module may bebetter suited for performing these operations faithfully and timely thanthe personnel, who may at times be distracted with other tasks, orforget or be unable to perform these operations faithfully or timely. Inparticular, manual transport by personnel may result in missed slides,slide breakage during handling, misplacement or misreading of slides bythe imager. In addition, in the case of slide storage, transport bypersonnel to the storage module can result in misplaced slides,incorrect documentation of slides stored within the storage moduleand/or costly and lengthy slide retrieval from the storage module.Advantageously, automated transport of the slides may allow improvedproductivity or throughput by reducing instrument downtime waiting forsamples to be transferred manually. Similar advantages can be offered byautomating the transfer of tissue blocks between microtomy module 307and storage module 314.

In one embodiment, transport module 302 may be a robotic device capableof transporting a slide between stations. In one embodiment, transportmodule 302 may be an X-Y-Z robotic device dimensioned to transport oneor more slides between stations. Representatively, transport module 302may be a track and elevator system. The track system may be a conveyorbelt or plate system that transports the slide horizontally in an “x-”direction. In this aspect, one or more slides may be placed on theconveyor and conveyed between the desired stations, for example, betweencoverslipper module 306, imager 308 and storage module 314. In oneembodiment, the conveyor belt system may have two separate conveyorbelts such that one conveyor belt transfers the slide in one directionand the other conveyor belt transfers the slide in the oppositedirection as illustrated by arrow 316. Alternatively, as described withreference to FIGS. 4-9, a single conveyor belt system may be used totransport the slide in more than one direction. Transport module 302 mayfurther include an elevator device. The elevator device transports theslide vertically in a y-direction when it is desired that a slide bepositioned at a location above or below the conveyor belt. The elevatordevice may further include a component for transporting the slide in andout of the elevator in the z-direction.

Staining module 304 and coverslipper module 306 may be an integratedslide stainer and coverslipping system. Alternatively, staining module304 and coverslipper module 306 may be in separate instruments atdifferent locations. In the case of an integrated system, stainingmodule 304 and coverslipper module 306 may be a staining/coverslippingsystem such as the TISSUE-TEK® PRISMA® and TISSUE-TEK® GLAS™ g2 combosystem or TISSUE-TEK® PRISMA® and TISSUE-TEK® FILM® combo systemcommercially available from Sakura Finetek U.S.A., Inc., Torrance,Calif. In one embodiment, staining module 304 may have hematoxylin andeosin stain (H&E) and special staining (SS) capabilities. At H&E/SSstaining and coverslipping, the biological sample may undergo H&E or SSstaining and optional coverslipping. Other staining or testing protocolsalso can be performed.

During operation, an individual slide or group of slides placed in abasket may be loaded into staining module 304 and stained according to adesired staining protocol. In the case of a group of slides, thestaining protocol can be the same for all slides or selected from astaining protocol menu, either by an operator or automatically byreading a bar code, an RFID or any other protocol identification device.Once the staining protocol is complete, the slide or group of slideswithin the basket is automatically transferred to coverslipper module306 for individual cover slipping. The identifier associated with eachslide is then read as the slides are coverslipped and either placed as agroup in a basket or individually fed onto transport module 302.

In an alternative embodiment, where a group of slides are stainedtogether, the slides may be singulated (separated from the group) instaining module 304 and placed on transport module 316. For example,where a group of slides are stained together in a basket, a pick andplace robotic device in staining module 304 may transfer the slidesindividually to transport module 316. From transport module 316, theslides may be conveyed to coverslipper module 306, or, without acoverslip, to one of imagers 308, 310, 312 or to storage module 314.

Imaging methods (quick-scan, 20×, 40×, z-stack, etc.) at imagers 308,310, 312 can be pre-assigned to each slide according to a laboratorydefault or specific instructions from, for example, a pathologist. Inthe case of basket-grouped slides, in one embodiment, each of the slideswould be assigned the same scanning method(s). Individual slides or thebasket of slides may be assigned to one of imagers 308, 310, 312 basedon the imagers availability or according to laboratory defined rules,such as dedicating one or more imagers to a specific scanning method(e.g., quick-scan, 20×, 40× or z-stack) or a plurality of methods.

In one embodiment, a slide including a biological sample is individuallytransported by transport module 302 to one of imagers 308, 310, 312and/or storage module 314. If the slide is ready for imaging (e.g.,dry), the system checks to see if, for example, imager 308 is available.Imager 308 is determined to be available if, for example, it is properlyfunctioning and not currently imaging another sample on a slide. Ifimager 308 is not available, the availability of imager 310 isdetermined. If imager 310 is not available, the availability of imager312 is determined. This process continues, until an available imager isfound. Alternatively, an imaging schedule between the slide and aparticular imager may be predetermined. Representatively, informationrelating to a period of time sufficient to allow the slide to dry may beassigned to the slide and imagers 308, 310 and 312 may be on an imagingschedule. The system may determine which imager will be available afterthe drying period expires. Once an available imager is determined, theslide is transported by transport module 302 to the available imager.Although three imagers are illustrated in FIG. 3, it is contemplatedthat fewer than three or more than three imagers may be included insystem 300.

If none of imagers 308, 310, 312 are available or there are otherconditions which require delay in imaging (e.g., waiting for slideprocessing instructions), transport module 302 transports the slide tostorage module 314. The slide remains in storage module 314 until one ofimagers 308, 310, 312 become available and/or processing instructionsare received. Once an imager is determined to be available, the slide istransferred from storage module 314 to transport module 302 using, forexample a robotic device, and transported by transport module 302 to theavailable imager for imaging. Upon completion of imaging, the slide maybe transported by transport module 302 from imager 308, 310 or 312 tostorage module 314. The image may be communicated to a diagnostician,for example a pathologist, for immediate examination. Via a computer(e.g., a personal computer), the pathologist can then examine an imageof a sample on a slide for viewing and recall a slide for more imagingwork if desired. Alternatively, if it is determined that no furtherexamination of the slide is desired, the slide may be removed from thestorage module 314.

In one embodiment, storage module 314 may include more than one storagemodule. In this aspect, one or more of the storage modules may act asshort-term storage areas for slides likely to need more imaging work. Inaddition, one or more of the storage modules may act as long-termstorage areas for slides which are unlikely to require more imaging workin the near future. The long-term storage modules may be located withinthe laboratory or remotely.

In one embodiment, storage module 314 is configured to group slides (andtissue blocks for the block storage system) according to user-definedcriteria. For example, slides pertaining to a patient case could beplaced in the same area. Then cases or blocks can be located by date ofproduction, by physician, by provenance, or by a combination of thesecriteria. Representatively, as noted above, a slide may contain anidentifier that may be read by a reader (e.g., RFID reader, bar codereader). That identifier (e.g., RFID, bar code) may contain information(e.g., letters, numbers and/or symbols) indicating a date of production,a physician and/or a provenance. When the information is read by areader, the information may be sent to the controller 400 or to otherdevices through the communications infrastructure.

Automated system 300 as illustrated in FIG. 3 provides fully automatedmovement of slides between staining module 304, coverslipper module 306,imagers 308, 310, 312 and storage module 314. In this aspect, system 300provides a seamless and continuous workflow which is in sync with otherlaboratory processes and eliminates the need for overnight processingand batching while reducing personnel errors and liabilities. It isfurther noted that there are no touch points from staining to storage insystem 300 therefore system 300 is believed to satisfy even the moststringent quality control programs such as Lean and Six Sigma.

FIG. 4 illustrates an embodiment of the system of FIG. 3. In thisembodiment, stainer module 304 is a TISSUE-TEK® PRISMA®stainer andcoverslipper module 306 is a TISSUE-TEK® FILM® coverslipper, bothcommercially available from Sakura Finetek USA. The TISSUE-TEK® PRISMA®stainer module and TISSUE-TEK® FILM® coverslipper module may beconnected to one another and a loading container used in thecoverslipper module to hold one or more racks of slides prior to acoverslipping operation may move between the coverslipper module 306 andstainer module 304. A brief description of the interaction between thesemodules is presented in the following paragraphs.

In order to automate the movement of the loading container in thecoverslipper module 306 between coverslipper module 306 and stainermodule 304, software instructions and a data link between coverslippermodule 306 and stainer module 304 are provided. Such instructions andlink may be solely between coverslipper module 306 and stainer module304. Alternatively, a control system may be connected to each ofstrainer module 304, coverslipper module 306, imagers 308, 310, 312,storage module 314 and transport module 302 that may be used totransport a slide between imagers and the modules. FIGS. 4-9 describecontroller 400 connected to each of the noted modules and imagers. Insuch case, instructions regarding the transfer and a data link may beestablished between the modules and imagers and the control system. Insuch case, controller 400 may control the transfer operations betweenstainer module 304 and coverslipper module 306. Controller 400 may alsocontrol (e.g., direct operation of) the various other modules andimagers as well as control slides relative to the modules and imagers.

Referring again to movement of a loading container from stainer module304 to coverslipper module 306, the loading container sits on a platethat is connected to wires that move the plate and the loading containerin an x- and y-direction, respectively, by two-step motors. The platemay move the loading container in an x-direction into the stainer.

In operation, a transfer arm of stainer module 304 retrieves a rack ofslides and moves the rack along an xy axis to one or more individualstaining stations. The transfer arm transfers a rack of slides to anappropriate staining station and then lowers the rack into that stainingstation for staining (a z-direction). Following staining, the transferarm removes the rack of slides from the staining station and moves in x-and y-direction to another staining station or, when all stainingoperations are complete, to a transfer station where the rack of slidesis to be transferred from the stainer to the Film® coverslipper module(coverslipper module 306).

For a transfer operation between stainer module 304 and coverslippermodule 306, the loading container in coverslipper module 306 receivesinstructions to move from coverslipper module 306 to stainer module 304through the adjacent doorways in each device. The loading container ismoved by the plate on which it sits along a single plane (xy plane) fromthe coverslipper to a position inside the stainer adjacent the doorwayof the stainer module. Once inside the stainer module, the transfer armlowers the rack of slides into the loading container. The loadingcontainer typically contains a solution such as xylene that wets theslides. The loading container then moves on the x-direction plate fromthe stainer into the coverslipper again through the adjacent doorways. Acover slipping operation including placing a film-type cover slip onindividual slides in the basket of slides is then performed in thecoverslipper.

Transport module 302 may be a robotic device capable of transporting aslide between stations. In the embodiment shown in FIG. 4, transportmodule 302 may be a robotic device including conveyor 402 that is aconveying system to transport a slide or group of slides horizontally ina loop between stainer module 304/coverslipper module 306, imagers 308,310, 312 and storage module 314. In this embodiment, conveyor 402transports a slide in one direction as illustrated by arrow 403 fromstainer module 304 or coverslipper module 306 to imagers 308, 310, 312and to storage module 314 and in an opposite direction as illustrated byarrow 405 from storage module 314 to imagers 308, 310 and 312. In oneembodiment, conveyor 402 may be a conveyor belt or a set of conveyingpallets disposed in a horizontal plane and dimensioned to transport aslide or group of slides. A conveying system that is a set of conveyingpallets may be similar to systems currently used in luggage carousels atcommercial airports. Such carousels typically include a deck that issurrounded by support wheel tracks. The support wheel tracks define apath that is frequently oval shaped. Evenly spaced along the wheeltracks are pallet support members. Attached to each end of the palletsupport members are support wheels. The support members are configuredto be transported along the support wheel tracks by the rolling of thesupport wheels. The support members are connected to each other at thetop by straps that run between support members. The bottoms areconnected to each other by rigid links. Thus, the support members, thesupport wheels, and the straps function in a manner analogous to a trainon endless railroad tracks.

Attached to the pallet support members are pallets. The pallets aredesigned to overlap one another and are secured to the pallet supportmembers to form a flexible surface. The overlap configuration of thepallets allows them to slide relative to each other as the palletstravel around the corners of the tracks. The leading edge of the palletsare secured to the support members by fasteners. Each of the pallets mayhave a slight bend to negotiate the curves in the unit.

In the embodiment shown in FIG. 4, conveyor 402 receives a slide fromcoverslipper module 306 and conveys the slide to one of imagers 308,310, 312. Referring to the TISSUE-TEK® FILM® coverslipper, coverslippermodule 306 individually places a film strip on a slide. With the systemdescribed in reference to FIG. 4, the slide is then moved to a dischargeposition in coverslipper module 306 and discharged onto conveyor 402from coverslipper module 306 onto conveyor 402. A discharge position incoverslipper module may be established at a position downstream of thecoverslipping operation. Referring to FIG. 4, a slide, such as slide424, is discharged onto conveyor 402 in a manner that its lengthdimension is disposed across a width dimension of conveyor 402. Reader423, such as an RFID or bar code reader, may be positioned at adischarge point onto conveyor 402 or downstream from a discharge pointto read an identifier on slide 424. Reader 423 is connected tocontroller 400 to indicate to controller 400 that slide 424 is onconveyor 402. Once delivered to conveyor 402, conveyor 402 conveys slide424 toward imagers 308, 310, 312.

As noted earlier, in this embodiment, multiple slides are brought toconverslipper module 306 from stainer module 304 in a rack. Incoverslipper module 306, the slides are singulated (separated from otherslides in a rack) for coverslipping. In one embodiment, all stainedslides in coverslipper module 306 are coverslipped. In anotherembodiment, a coverslipping operation may be bypassed. Such bypass canoccur at the singulation point in coverslipper module 306. According tothis embodiment, a slide is singulated and either directed to bedirectly discharged onto conveyor 402 or to be coverslipped and thendischarged.

In one embodiment, a slide retaining device is positioned adjacent to orconnected to conveyor 402. Slide retaining device 420, in oneembodiment, is an oval-shaped chain or belt (e.g., a continuous loop)having projections 422 extending outwardly therefrom. Projections 422are spaced from one another at approximately a width of a slide.

As shown in FIG. 4, stainer module 304, coverslipper module 306 andimagers 308, 310, 312 are positioned on one side of conveyor 402. Slideretaining device 420 is positioned on a side of conveyor 402 opposite tothe side including stainer module 304, coverslipper module 306 andimagers 308, 310, 312. Projections 422 of slide retaining device 420project outward in a direction toward conveyor 402. A length of slideretaining device 420 is positioned adjacent conveyor 402 so thatprojections 422 extend a distance on to conveyor 402. In one embodiment,slide retaining device 410 is a synthetic rubber or other plasticmaterial with projections 422 of similar preferably resilient material.Projections 422 have a thickness of 0.5 millimeters (mm) or less, suchas 0.25 mm, and a length of 0.5 mm to 1 mm. Slide retaining device 420projects above the plane defined by conveyor 402 a distance sufficientto allow a length of projections 422 to lay on conveyor 422 or slightlyabove (e.g., less than 0.25 mm above) conveyor 422. In this manner, aslide may be retained on conveyor 402 between two adjacent projections422.

Slide retaining device 420 is rotated by a pulley and moves at the samerate as conveyor 402. FIG. 5 shows a side view of the system of FIG. 4through line 5-5′. As shown in FIG. 5, slide retaining device 420 isconnected at one looped end to pulley 430 and the other looped end topulley 430. Pulley 430 rotates on axle 435. Axle 435 extends a width ofconveyor 402 to an opposite side where a second end of axle 435 isconnected to pulley 437. Pulley 437 is connected through a belt topulley 440 that drives conveyor 402.

As illustrated in FIGS. 4-6 and 7, slides, such as slide 424 aredischarged from coverslipper module 306 or optionally stainer module 204individually and are placed on conveyor 402. Conveyor 402 may bepositioned, for example, slightly below exit port 407 of coverslippermodule 306 (and optional exit port 409 of stainer module 304) so thatslides are placed onto conveyor 402 via gravity. Ideally, a slide isplaced on conveyor 402 between two projections 422 of slide retainingdevice 420. However, where a slide is not aligned between projections422 as the slide exits coverslipper module 306, a force of a projectionagainst an edge of a slide is sufficient to re-position a slide betweenprojections.

Conveyor 402 transports a slide to imagers 308, 310, 312. Imagers 308,310, 312 are, for example, digital imagers and may further each containa reader (e.g., RFID reader, bar code reader) connected with controller400 to read an identifier on a slide indicate to controller 400 that aslide is in the imager and to associate a digital image with theidentifier. In one embodiment, conveyor 402 stops at each imager andcontroller 400 assesses the availability of the imager (e.g., receives asignal that indicates whether or not an imager is available). If animager is available and control system (e.g., controller 400) determinesthat a slide may be imaged at this time (e.g., the slide is dry), theslide is placed in the imager.

In one embodiment, a slide is placed in an imager by applying a pushingforce to the slide. In this embodiment, associated with each imager 308,310, 312 and controlled by controller 400 is a plunger assembly. FIGS.4-7 show plunger assembly 408, 410 and 412 associated with imagers 308,310, 312, respectively. Plunger assembly 408, 410 and 412 are positionedon a side of conveyor 402 opposite imagers 308, 310 and 312.

Each plunger assembly 408, 410, 412 includes an actuator such as anelectrical motor or air piston that drives a corresponding plunger toextend or retract. A plunger, when actuated, moves outward from theplunger assembly toward the respective imager. The plunger may be a baror rod having a thickness equivalent to or greater than a thickness of aslide. Each plunger assembly is positioned adjacent conveyor 402 suchthat when a plunger is extended from a plunger assembly, the plungerwill contact a surface of conveyor 402 or extend over conveyor 402 aslight distance (e.g., 0.1 to 0.25 mm). Plunger must be close enough toconveyor 402 that it is capable of contacting an edge of a slide on theconveyor and pushing the slide off conveyor 402 as it extends. To theextent a height of slide retaining device 420 would otherwise prevent aplunger form contacting an edge of a slide, plunger is made of amaterial having sufficient weight or density to deflect slide retainingdevice 420. For example, a plunger comprised of a steel bar or rod canbe made of a sufficient weight to deflect slide retaining device 420 ofa synthetic rubber belt downward. In another embodiment, a plunger mayextend from a plunger assembly at an angle slightly less than horizontal(e.g., less than 5°) so that the plunger will deflect slide retainingdevice 420 to be at most parallel with a surface of conveyor 402.

If a slide is positioned in front of the imager (imagers 308, 310, 312)and the imager is available, the plunger will push the slide intoimager. Thus, the plunger is oriented such that it will contact an edgeof a slide on conveyor 402. FIG. 7 shows an illustration of a slidepushed from conveyor 402 into imager 308. FIG. 7 shows plunger 458actuated from plunger assembly 408 and extending across conveyor 402.The actuation of plunger 458 causes plunger 458 to contact slide 424 andpush slide 424 into imager 308. A cut-away view of imager 308 showsslide 424 on a stage or imaging platform within imager 308 and ready forimaging. The cut-away view also shows plunger assembly 488 on a side ofa stage or imaging platform opposite plunger assembly 488. Plungerassembly 488 is configured to push slide 424 from inside imager 308 backonto conveyor 402 once imaging of slide 475 is complete.

As noted above, in one embodiment, controller 400 is connected tostainer module 304, coverslipper module 306, imagers 308, 310, 312,plunger assemblies 408, 410, 412, corresponding plunger assembliesassociated with each imager, storage module 314 and conveyor 402. Inaddition to optionally controlling a staining of slides in stainermodule 304 and coverslipping slides in coverslipper module 306,controller 400 includes instructions (e.g., a computer program) forcontrolling a discharge of a slide from coverslipper module 306 or,optionally, stainer module 304 onto conveyor 402 and the movement ofconveyor 402 to bring a slide to imagers 308, 310, 312.

To control discharging of a slide onto conveyor 402 from coverslippermodule 306, controller 400 receives data from coverslipper module 306whether a slide is ready for discharge. In one embodiment, this data isprovided to controller 400 in the form of a signal when a slide ispositioned in a designated area in coverslipper module 306. The slidemay or may not have proceeded through a coverslip operation incoverslipper module 306. Controller 400 checks to see if a position onconveyor 402 is free to receive a slide. In the embodiment shown inFIGS. 4-7, the system includes sensor 495 positioned approximately oneslide width upstream of exit port 416 of coverslipper module 306. Sensor495 may be, for example, a photoelectric sensor that sends a light beamacross a surface of conveyor 402. When the beam is broken, a sensorsends a signal to controller 400 that a slide is present. It isappreciated that, in an embodiment where a slide may be discharged fromstainer module 304, a similar technique may be employed with, forexample, a sensor similar to sensor 495.

In one embodiment, control system stops conveyor 402 for a brief moment(e.g., three to five seconds) in periodic intervals each time a slidecould be positioned in front of an imager. Controller 402 receives asignal whether the imager is available for receiving a slide forimaging. It may receive this signal in an unsolicited fashion (e.g., asensor associated with the sensor sends a signal whenever the imager isavailable) or it may solicit the signal (e.g., controller sends a signalto a sensor associated with the imager and receives a reply to the sentsignal from the sensor). If a slide is present on conveyor 402 and animager is available, control system will activate a correspondingplunger assembly to place a slide in the imager. Similarly, controller400 checks when an imaging of a slide is complete and subsequentlydischarges the slide onto conveyor 402. In one embodiment, a sensor suchas a photoelectric sensor may be associated with, including connected oradjacent to, each of plunger assembly 408, 410, 412 to sense whether aslide is present on conveyor 402 or conveyor 402 is free to receive aslide from imagers 308, 310, 312. FIG. 6 shows sensor 496 connected toimager 408. In one embodiment, a corresponding sensor component may beconnected to imager 308 directly across from sensor 496. Alternatively,a memory associated with controller 400 may track the position of slideson conveyor 402 based on data supplied by sensor 495 and by coverslippermodule 306, and with this data, compute whether conveyor 402 is free toreceive a slide from imagers 308, 310, 312. The brief stoppage ofconveyor 402 also may be utilized to assess whether a slide is onconveyor 402 upstream of an exit port of coverslipper module 306, suchas based on data received from sensor 495.

Although plunger assemblies are described for transferring slidesbetween conveyor 402 and imagers 308, 310, 312, it is contemplated thatany other type of robot device suitable for transferring a slide betweenprocessing stations may be used. Representatively, a robotic arm capableof grasping slide 424 and transferring slides between imagers 308, 310,312 and conveyor 402 may be used. For example, in embodiments where agroup of slides are transported within a basket, slides must be removedindividually from the basket for imaging. In this aspect, a Gantry orCartesian coordinate type robot, a selective compliant assembly robotarm (SCARA) type robot, an articulated arm type robot, or a combinationthereof (e.g., a SCARA type robot coupled in a Gantry type robotconfiguration) may be used to retrieve and deposit individual slideswithin the basket.

In one embodiment described with reference to FIGS. 3-7, stainer module304 and coverslipper module 306 are connected and slides are conveyed bystainer module 304 to coverslipper module 306 through a commerciallyavailable integrated system, although in another embodiment, suchconveyance can alternatively be controlled by controller 400 as part ofan overall control system. In another embodiment, slides may betransferred from stainer module 304 to conveyor 402 and then conveyedvia conveyor 402 to coverslipper module 306 using, for example, aplunger assembly(ies) such as described above or other type of transfermechanism.

FIGS. 4-7 also show conveyor 402 extending into storage module 314. Inone embodiment, conveyor 402 has a continuous loop shape with one end ofthe loop extending into and out of storage module 314.

FIG. 8 illustrates a cross-section of storage module 314 through line8-8′ of FIG. 4. In one embodiment, storage module 314 may include atleast one of a drawer, chamber, compartment, cabinet, enclosure,cubbyhole, or the like. A robotic device such as transport module 302may be capable of introducing a slide into storage module 314, andremoving the slide from storage module 314, for example, via conveyor402. Storage module 314 may further include a door which may be accessedby transport module 302.

In an embodiment where storage module 314 is a cabinet, storage module314 may have a plurality of slide stations 602. Each of slide stations602 may be dimensioned to receive and store a slide. In one embodiment,slide stations 602 are dimensioned to receive and store a slideindividually or a group of slides. In the case of a group of slides, theslide group may be stored in slide stations 602 in a tray or basket. Forexample, a tray or basket holding 10 slides may be stored within one ofslide stations 602. In this aspect, slide stations 602 are dimensionedto store the tray or basket having the sides therein.

In one embodiment, stations 602 may be formed in a grid pattern asillustrated in FIG. 8. Slides stored within stations 602 may be locatedand retrieved from storage 314 using an indexing system including, forexample, coordinates corresponding to the grid pattern.Representatively, each column may be assigned an identifier and each rowmay be assigned a different identifier from that of the columns. Forexample, the first column starting from the left hand side of storagemodule 314 may be assigned the identifier “1” and the first row startingat the top of storage module 314 may be assigned the identifier “A.” Inthis aspect, the location of station 602A may be A1. A slide storedwithin station 602A may be assigned location A1. When it is desired toretrieve the slide, the system is directed to retrieve the slide atlocation A1. In other embodiments, slide stations 602 may be verticallystacked compartments within storage module 314.

Transport module 302 may include one or more elevator devices positionedin storage module 314 to place slides within or retrieve slides fromslide stations 602 and transfer slides between slide stations 602 andconveyor 402.

Elevator device 614 may be used to move the slide vertically betweenconveyor 402 (a y-direction in reference to FIG. 4). Elevator device 614also includes track member 604 which allows for movement of frame memberhorizontally in a z-direction (with reference to FIG. 4) as illustratedby arrow 606. Elevator device 614 may be positioned between conveyorbelt 402 and slide stations 602. Elevator device 614 may include framemember 618 and lift member 620 which travels along frame member 618. Amotor and pulley system may be connected to frame member 618 and liftmember 620 to drive lift member 620 along frame member 618.

Elevator device 614 may further include slide platform 622 positionedwithin lift member 620. Slide platform 622 may be movably coupled tolift member 620 such that it slides horizontally in an x-direction toeject the slide from or receive the slide within elevator device 614.Slide platform 622 is dimensioned to receive and retain slide 624 withinlift member 620. In one embodiment, slide platform 622 may be arectangularly shaped box having open ends and of a size configured tocontain a single slide (e.g., 1 in.×1 in×3 in.). Slide platform 622 maybe at least as wide as a width of the slide so that the slide may bepositioned thereon. The slide may be inserted into and retrieved througheither side of slide platform 622. Alternatively, slide platform 622 maybe a planar member (a true platform) upon which the slide can besupported by slide platform 622.

Elevator device 614 may be used to transfer slide 624 between conveyor402 and slide stations 602. Representatively, conveyor 402 may transportslide 624 from, for example, coverslipper module 306 or imagers 308,310, 312, to slide stations 602. Conveyor 402 moves slide 624horizontally in the x-direction until slide 624 is aligned with slideplatform 622. In this aspect, lift member 620 moves vertically in they-direction along frame member 618 until slide platform 622 is alignedwith slide 624. Once slide platform 622 is aligned with slide 624, slideplatform 622 moves in the x-direction toward conveyor 402 until it ispositioned around slide 624. In one or more embodiments, slide platform622 may include pincers, claws, jaws, hook-like structures or anothergripping member. Slide platform 622 then moves in the opposite direction(i.e., away from conveyor 402) with slide 624 inside. Lift member 620raises slide platform 622 having slide 624 therein until slide 624 isaligned with opening 428 of slide stations 602. Slide platform 622 thenmoves in the “X” direction toward slide stations 602 to insert slide 624within the opening of the slide station. Once slide 624 is within theopening, slide platform 622 releases slide 624 and retracts (i.e. movesaway from slide stations 602) thereby leaving slide 624 within slidestations 602 for storage.

Once storage is complete, elevator device 614 may be used to removeslide 624 from slide stations 602 and place it back on conveyor 402 fortransport to, for example, imagers 308, 310, 312.

Although elevator device 614 is described for transferring slide 624between conveyor 402 and slide stations 602, it is contemplated that anyother type of robot device suitable for transferring a slide betweenprocessing stations may be used. Representatively, a robotic arm capableof grasping slide 624 and transferring slide 624 between slide stations602 and transport module 302 may be used. For example, in embodimentswhere a group of slides are transported within a basket, slides must beremoved individually from the basket for imaging. In this aspect, aGantry or Cartesian coordinate type robot, a selective compliantassembly robot arm (SCARA) type robot, an articulated arm type robot, ora combination thereof (e.g., a SCARA type robot coupled in a Gantry typerobot configuration) may be used to retrieve and deposit individualslides within the basket.

As previously discussed, a slide may be inserted and stored in any ofstations 602 which are positioned in a grid pattern. In this aspect, therobotic device for inserting and retrieving the slides must be able tomove both vertically in the y-direction and horizontally in thex-direction. To store a slide or retrieve a slide stored in station602A, lift member 620 of elevator device 614 moves vertically asillustrated by arrow 616 up to the top row (e.g. row A) of storagemodule 314. Frame member 618 then moves horizontally as illustrated byarrow 606 to the first column (e.g., column 1).

To store slide 424 within station 602A, slide platform 422 moves in the“z-” direction toward storage module 314 and inserts slide 424 withinstation 602A. Once slide 424 is positioned within station 602A, slideplatform 622 moves in a direction away from storage module 314 leavingslide 624 behind within station 602A. To retrieve slide 624 from station602A, slide platform 622 is inserted within station 602A and aroundslide 624. Movement of slide platform 622 away from station 602A pullsslide 624 out of station 602A and into elevator device 614. Lift member620 of elevator device 614 may then be raised or lowered to transferslide 624 to conveyor 402. Conveyor 402 may then be used to convey slide624 to imager 308, 310, 312.

The identification, placement and retrieval of a slide within storagemodule 314 may be controlled by controller 400 that is electrically orcommunicatively linked to transport module 302. In one or moreembodiments, movement or operation of transport module 302 may be basedon signals exchanged between the controller and storage module 312. Forexample, in one embodiment, such a controller may receive a signal fromcoverslipper module 306 indicating that a slide is ready for storage. Inresponse, the controller may signal transport module 302 to retrieve theslide from the coverslipper module and transfer the slide to storagemodule 314. A reader (e.g., an RFID or bar code reader) may bepositioned at the entrance to storage module to read an identifierassociated with the slide. This information is transmitted to controller400. The controller may identify an open slide station within storagemodule 314 and signal transport module 302 to insert the slide withinthe open slide station. The slide location information may be stored bythe system. In one embodiment, the slide location may be selected basedon a criteria such as patient case, a physician or hospital, term ofstorage, etc. When retrieval of the slide is desired, for example wherea pathologist instructs the system to perform further imaging of theslide, controller 400 may determine the location information of thedesired slide and signal transport module 302 to retrieve the slide fromthe appropriate slide station within storage module 314.

FIG. 9 illustrates a perspective view of the storage module and elevatordevice of FIG. 8. From the view in FIG. 9, it can be seen that liftmember 620 slides vertically along track 702 formed in lift member 620.In this aspect, lift member 620 may have protrusions along its outersurface that line up with and may be engaged within track 702.Similarly, track member 604 includes tracks 704 along which frame member618 slides.

FIG. 8 and FIG. 9 describe a storage module in connection with storingslides. In another embodiment, a storage module is configured to storeslides as well as tissue blocks (e.g., tissue blocks containing anidentifier tag). In another embodiment, the system includes storagemodule 202 for storing slides and a separate storage module for storingtissue blocks. A storage module to store tissue blocks may be configuredsimilar to storage module 314, including an identifier reader, andlinked to controller 400. In either configuration, controller 400 isconfigured to store identification information of the slides and tissueblocks so that a slide(s) may be linked to a tissue block. FIG. 4 showsmicrotomy module 307 adjacent conveyor 402. Microtomy module may includetissue block processing equipment including a microtome and anidentifier reader linked to controller 400. In one embodiment, tissueblock may be loaded onto conveyor 402 from microtomy module 307 (orunloaded from conveyor 402 to microtomy module 307) or loaded/unloadedstorage module 314 to conveyor 402 or vice versa similar to the methodsdiscussed above for loading/unloading slides.

An automated system for slide transport between processing stations isdisclosed. One skilled in the art will appreciate that the presentinvention can be practiced by other than the preferred embodiments whichare presented in this description for purposes of illustration and notof limitation, and the present invention is limited only by the claimsthat follow. It is noted that equivalents for the particular embodimentsdiscussed in this description may practice the invention as well.Representatively, in one embodiment, a “Reflex Staining” procedure maybe implemented. In that procedure, the system recommends specificstaining and/or testing of biological samples based on patternrecognition reports of an interpretation module. The reflex stainer mayinclude a staining system, imager and interpretation module, which aregrouped together and implemented as a single automated instrument.Alternatively, they may be in separate instruments at differentlocations. Processing may be performed by instruments both inside andoutside the reflex stainer, such as for example in grossing, processingand embedding, microtomy and staining and coverslipping.

In some embodiments, the above-described transport module may beimplemented in connection with tissue block processing.Representatively, a sample of tissue, which has potentially been grossedand/or fixated in a block of paraffin, may be transported by thetransport module between a microtome, imager and storage module. Forexample, the block having the tissue embedded therein and an identifiermay be sectioned by the microtome and then transported to the storagemodule. If, upon examination of the tissue section, it is determinedthat another tissue section is needed, a controller may signal thetransport module to retrieve the block from the storage module andtransport it back to the microtome for additional sectioning.

One or more embodiments of the invention may be provided as a programproduct or other article of manufacture that may include amachine-readable computer medium having stored thereon one or moreinstructions. The medium may provide instructions, which, if executed bya machine such as a robot or integration unit, may result in and/orcause the machine to perform one or more of the operations or methodsdisclosed herein. Suitable machines include, but are not limited to,robots, integration units, computer systems, laboratory equipment, and awide variety of other machines, to name just a few examples.Representatively, the medium may include recordable mediums, such as,for example, floppy diskette, optical storage medium, optical disk,CD-ROM, magnetic disk, magneto-optical disk, read only memory (ROM),programmable ROM (PROM), erasable-and-programmable ROM (EPROM),electrically-erasable-and-programmable ROM (EEPROM), random accessmemory (RAM), static-RAM (SRAM), dynamic-RAM (DRAM), Flash memory, othertypes of memory, other machine-readable medium within programmable logicunits used to control robots, and combinations thereof.

It should also be appreciated that reference throughout thisspecification to “one embodiment”, “an embodiment”, or “one or moreembodiments”, for example, means that a particular feature may beincluded in the practice of the invention. Similarly, it should beappreciated that in the description various features are sometimesgrouped together in a single embodiment, Figure, or description thereoffor the purpose of streamlining the disclosure and aiding in theunderstanding of various inventive aspects. This method of disclosure,however, is not to be interpreted as reflecting an intention that theinvention requires more features than are expressly recited in eachclaim. Rather, as the following claims reflect, inventive aspects maylie in less than all features of a single disclosed embodiment. Thus,the claims following the Detailed Description are hereby expresslyincorporated into this Detailed Description, with each claim standing onits own as a separate embodiment of the invention.

In the foregoing specification, the invention has been described withreference to specific embodiments thereof. It will, however, be evidentthat various modifications and changes can be made thereto withoutdeparting from the broader spirit and scope of the invention as setforth in the appended claims. The specification and drawings are,accordingly, to be regarded in an illustrative rather than a restrictivesense.

1. An apparatus comprising: at least one of a stainer module and acoverslipper module; an imaging module; a storage module; an automatedtransport module for transporting at least one slide between the atleast one of the stainer module and the coverslipper module, the imagingmodule and the storage module, the transport module capable oftransporting the at least one slide in at least two differentdirections; a reader associated with the automated transport module, thereader capable of reading an identifier positioned on the at least oneslide being transported by the automated transport module; and acontroller for directing transport of the at least one slide by thetransport module, wherein the controller is in communication with thereader and reading of the identifier by the reader indicates to thecontroller that the at least one slide is on the automated transportmodule.
 2. The apparatus of claim 1, wherein the storage modulecomprises an indexing system for identifying a location of the at leastone slide within the storage module.
 3. The apparatus of claim 1,wherein the storage module comprises a plurality of slide storagestations.
 4. The apparatus of claim 1, wherein the transport modulecomprises at least one of a conveyor belt or a set of conveyor palletsdisposed in a horizontal plane.
 5. The apparatus of claim 4, wherein thetransport module comprises a conveyor configured for bi-directionaltransport.
 6. The apparatus of claim 1 wherein the imaging modulecomprises a plurality of imaging modules.
 7. The apparatus of claim 1,wherein the imaging module is a charge coupled device (CCD).
 8. Theapparatus of claim 1, wherein the controller comprises machine readableinstructions that, when executed by the controller, cause the controllerto place a slide in the imaging module when the imaging module isavailable for receiving a slide.
 9. The apparatus of claim 1, whereinthe controller comprises machine readable instructions that, whenexecuted by the controller, cause the controller to retrieve a slidefrom the storage module and transport the slide to the imaging module.10. The apparatus of claim 1, wherein the storage module is a slidestorage module, the apparatus further comprising: a tissue block storagemodule.
 11. The apparatus of claim 10, wherein the slide storage moduleand the tissue block storage module are integrated.
 12. The apparatus ofclaim 10, wherein the controller comprises machine readable instructionsthat, when executed by the controller, cause the controller to retrievea tissue block from the tissue block storage module.